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News Review

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HEPATITIS JOURNAL REVIEW:
A Bi-Monthly Publication of the Hepatitis Support Project

July 25 , 2005 Volume 2, Issue 11


Liz Highleyman

To download pdf version click here


In This Issue: Hepatitis C

No Benefit to Individualized Therapy

Post-Transplant Treatment

HIV/HCV Coinfection News

Hepatitis C in California Prisons


No Benefit to Individualized Therapy

Given the wide range of virus and host (patient) factors that can influence the progression of hepatitis C and response to therapy, experts have explored whether individually tailored treatment might improve outcomes. In the August Journal of Hepatology, Stefan Zeuzemand colleagues with the DITTO-HCV Study Group reported on an international trial comparing individualized versus standard treatment in patients with chronic hepatitis C. In this randomized, controlled trial, researchers studied 268 chronic HCV patients treated with pegylated interferon (Pegasys) plus ribavirin. After six weeks of therapy, the subjects were classified as rapid, slow, flat, or null responders. Then, patients within each of these groups were randomly assigned to received continued standard therapy or one of four individualized regimens: 1) Pegasys monotherapy for 48 weeks or Pegasys/ribavirin for 24 weeks for rapid responders; 2) triple therapy with Pegasys/ribavirin plus histamine for 48 weeks or prolonged Pegasys/ribavirin for 72 weeks for slow responders; 3) triple therapy for flat responders; and 4) high-dose Pegasys (360 mcg/week) plus ribavirin for null responders. The overall end-of-treatment response rate was 77% in both the standard and individualized arms. Respective sustained virological response (SVR) rates were 66% and 60%. The addition of histamine did not improve response rates. The authors concluded that, “[A]n improvement in virologic efficacy was not achieved with the available individualized treatment options.”

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Post-Transplant Treatment

One of the limitations of liver transplantation for people with hepatitis C is that HCV usually reinfects the new donated liver. Fortunately, a recent study suggests that treatment during the acute phase of HCV recurrence can produce successful outcomes. In the July Journal of Hepatology, Llus Castells and colleagues reported on a study of 48 patients with genotype 1b HCV who received transplants due to liver cirrhosis. Half the subjects were treated in the acute phase of recurrent HCV with pegylated interferon (Peg-Intron, 1.5 mcg/kg) plus ribavirin for at least 24 weeks. More than half the treated patients (58%) had undetectable HCV viral load at the end of treatment and 35% achieved SVR, compared with none of the untreated subjects. Side effects included anemia (71%) and leukopenia (96%). The authors concluded that “[t]he combination was safe, with a low rate of therapy withdrawal.” The SVR rate in this study was significantly lower than the high rates (75% or better) seen in non-transplant patients with acute HCV. But while HCV is rarely detected early enough to allow for acute-phase treatment under normal circumstances, post-transplant patients may be closely monitored for HCV recurrence, allowing treatment to begin as soon as possible.



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HIV/HCV Coinfection News
In the June AIDS Research and Human Retroviruses, Amanda Mocroft and colleagues with the international EuroSIDA study analyzed why HIV positive patients stopped taking their initial combination antiretroviral therapy (HAART) regimens. The analysis included 1,198 patients who started HAART after 1999. One year after starting HAART, 70% of patients remained on their original regimen, 24% had changed, and 6% had stopped all anti-HIV treatment. The most frequent reason for discontinuation was toxicities (30%). The researchers found that HIV positive patients coinfected with HCV were about one-and-a-half times more likely than HIV monoinfected subjects to discontinue HAART due to toxicity, and were also more likely to stop due to patient or physician choice. They concluded that “[m]anaging adverse events must remain a key intervention” in order to help coinfected patients stay on HAART.

In related news, D. Salmon-Ceron and colleagues reported in the June Journal of Hepatology that liver disease is a major cause of death among HIV-infected individuals, confirming several previous studies showing an increasing impact of liver disease on HIV-related morbidity and mortality since the advent of HAART. The researchers examined the year 2000 death record from 185 French hospital departments that provide HIV/AIDS care. They found that a mong 822 HIV-infected patients, 29% were infected by HCV alone, 8% by HBV alone, and 4% by both HCV and HBV. The most frequent causes of death among HIV/HCV coinfected patients were liver disease (31%) and AIDS (29%); among those with HIV/HBV coinfection, the leading causes were AIDS (38%) and liver disease (22%). Among those triply infected with all three viruses, liver disease accounted for 44% of deaths. Hepatocellular carcinoma was present in 15% of patients who died from liver disease, and was associated with HBV coinfection. Nearly half the patients who died from liver disease had more than 200 CD4 cells, indicating that even individuals with relatively intact immune systems are at risk.

Finally, in the June 15 Clinical Infectious Disease, G. Antonucci and colleagues from Italy reported on a study looking at how HCV coinfection affects immune recovery after starting HAART. They analyzed data from 284 HCV positive and 1,219 HCV negative subjects with HIV starting their first antiretroviral regimen. As in some earlier studies, the researchers found that HCV negative subjects were more likely to achieve a CD4 count increase of at least 100 cells – and to do so faster – compared with HCV positive individuals. The likelihood of achieving a CD4 count increase of 100 cells or more was not significantly associated with HCV viral load or genotype, but further analysis revealed that patients with genotype 3 were less likely to achieve a CD4 count of 300 cells. “ Results of our large, prospective study support a direct role of HCV viremia in the CD4 cell count response to HAART,” the authors concluded. “Moreover, our results underline the fact that, in individuals coinfected with HIV and HCV, the goal of treating HCV infection is to eradicate HCV, to both slow the rate of HCV progression and limit potential interference with the response to HAART.”



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Hepatitis C in California Prisons

R. Fox and colleagues studied the prevalence of and risk factors for hepatitis C in the California state correctional system; their results were reported in the July 15 Clinical Infectious Diseases. The researchers conducted structured interviews with 469 prisoners entering the system and screened them for HCV antibodies. The prevalence of HCV infection was 34% overall. The likelihood of having HCV was strongly associated with injection drug use: 66% among those with a history of injection drug use, compared with 10% among those with no such history. Other factors independently linked to HCV infection included age, cumulative time of incarceration, sex (men were more likely to be infected than women), and a history of having sex with a male IDU. Among non-IDUs, factors associated with HCV infection included receiving blood product transfusions and cumulative years of incarceration. The authors concluded that, “HCV infection is pervasive among the California prison population, including prisoners who are non-IDUs and women with high-risk sexual behavior.” Because not all infected individuals had traditional HCV risk factors, the researchers suggested that routine HCV antibody screening and behavioral interventions should be instituted for all incarcerated men and women.


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